Medicine and Health Sciences Commons^™

Accumulation Of Rhodopsin In Late Endosomes Triggers Photoreceptor Cell Degeneration, Yashodhan Chinchore, Amitavo Mitra, Patrick J. Dolph, Norbert Perrimon

Dartmouth Scholarship

Progressive retinal degeneration is the underlying feature of many human retinal dystrophies. Previous work using Drosophila as a model system and analysis of specific mutations in human rhodopsin have uncovered a connection between rhodopsin endocytosis and retinal degeneration. In these mutants, rhodopsin and its regulatory protein arrestin form stable complexes, and endocytosis of these complexes causes photoreceptor cell death. In this study we show that the internalized rhodopsin is not degraded in the lysosome but instead accumulates in the late endosomes. Using mutants that are defective in late endosome to lysosome trafficking, we were able to show that rhodopsin accumulates …

Detailed Analysis Of Sequence Changes Occurring During Vlse Antigenic Variation In The Mouse Model Of Borrelia Burgdorferi Infection, Loïc Coutte, Douglas J. Botkin, Lihui Gao, Steven J. Norris

Faculty, Staff and Student Publications

Lyme disease Borrelia can infect humans and animals for months to years, despite the presence of an active host immune response. The vls antigenic variation system, which expresses the surface-exposed lipoprotein VlsE, plays a major role in B. burgdorferi immune evasion. Gene conversion between vls silent cassettes and the vlsE expression site occurs at high frequency during mammalian infection, resulting in sequence variation in the VlsE product. In this study, we examined vlsE sequence variation in B. burgdorferi B31 during mouse infection by analyzing 1,399 clones isolated from bladder, heart, joint, ear, and skin tissues of mice infected for 4 …

Automated Identification Of Relative Clauses In Child Language Samples, Hali Anne Michaelis

Theses and Dissertations

Previously existing computer analysis programs have been unable to correctly identify many complex syntactic structures thus requiring further manual analysis by the clinician. Complex structures, including the relative clause, are of interest in child language samples due to the difference in development between children with and without language impairment. The purpose of this study was to assess the comparability of results from a new automated program, Cx, to results from manual identification of relative clauses. On language samples from 10 children with language impairment (LI), 10 language matched peers (LA), and 10 chronologically age matched peers (CA), a computerized analysis …

Dna Instability In Replicating Huntington's Disease Lymphoblasts, Milena Cannella, Vittorio Maglione, Tiziana Martino, Giuseppe Ragona, Luigi Frati, Guo-Min Li, Ferdinando Squitieri

Toxicology and Cancer Biology Faculty Publications

BACKGROUND: The expanded CAG repeat in the Huntington's disease (HD) gene may display tissue-specific variability (e.g. triplet mosaicism) in repeat length, the longest mutations involving mitotic (germ and glial cells) and postmitotic (neurons) cells. What contributes to the triplet mutability underlying the development of HD nevertheless remains unknown. We investigated whether, besides the increased DNA instability documented in postmitotic neurons, possible environmental and genetic mechanisms, related to cell replication, may concur to determine CAG repeat mutability. To test this hypothesis we used, as a model, cultured HD patients' lymphoblasts with various CAG repeat lengths.

RESULTS: Although most lymphoblastoid cell lines …

Download The Pdf Of The Full Issue

CenterPieces

Download the PDF of the Full Issue of CenterPieces, Fall 2007, Volume 2, Issue 1.

We Are Seeking Participants For The Following Studies

CenterPieces

All participants in our research projects receive compensation for participating in study interviews. For further information about these and other studies, please visit our website at www.jefferson.edu/jchp/carah or call 215-503-2897 to speak to a member of our staff.

Coping Tips For Caregivers

CenterPieces

Educate yourself about the disease your family member is facing and how it may affect his or her behavior, pain level or quality of life.

Find sources of help for caregiver tasks. Contact family, friends, neighbors, church/synagogue, workplace, Area Agency on Aging or other organizations.

Protect your personal time for something you enjoy or something you need to get done.

Helping Caregivers To Cope

CenterPieces

When Deb Lacktman promised her dying father that she would care for her mother, Margaret Rimato, after he passed, she wasn’t prepared for the challenges to come. Shortly after he passed, Margaret became increasingly forgetful and delusional. Deb attributed her mother’s memory loss to the stress of losing her husband. With time, however, Margaret’s condition worsened and she was diagnosed with Alzheimer’s disease.

As the primary caregiver of a parent with Alzheimer’s, Deb dealt with various complications beyond the memory loss. Her mother continually roamed the house in the middle of the night, for no apparent reason. It turned out …

Speaking With Barry Rovner, Md

CenterPieces

Q: What Alzheimer’s related studies are you involved in currently at the Farber Institute for Neurosciences?

Dr. Rovner: We are evaluating three exciting new disease-modifying drug treatments that may slow down the course of Alzheimer’s disease. I am also a Principal Investigator of Jefferson’s Center for Excellence in Neurodegenerative Diseases funded by the Pennsylvania Department of Health Tobacco Settlement grant. We are testing innovative screening methods to identify dementia in community-based agencies serving older adults, as well as testing in-home skills training services to delay nursing home placement and reduce stress for a racially diverse group of family caregivers. This …

Message From Dr. Laura Gitlin, Director Of Carah, Laura N. Gitlin

CenterPieces

Welcome to the second issue of CenterPieces, the newsletter of the Center for Applied Research on Aging and Health. We dedicate this issue to the topic of dementia and family caregiving, a critical public health issue. There are 26 million individuals with dementia worldwide, and approximately 5 million individuals with the diagnosis in the US. This number may exceed 16 million in 2050.

For the past 15 years, CARAH has been in the forefront of developing and testing innovative approaches to supporting families in their heroic care efforts and enhancing the quality of life of affected individuals. CARAH’s current research …

Today - February 9, 2009, Loma Linda University

TODAY

Inside this issue:

-- LLUMC ranks high in Nursing Professionals magazine’s list of top hospitals to work for
-- LLU tobacco control trainees graduate in Cambodia
-- Young Redlands entrepreneur’s efforts benefit kids at LLUCH
-- Dressing Up Red set for Sunday, February 15
-- LLUAHSC Councilors sponsor Friday evening vespers concert
-- LLUCH becomes nation’s first hospital to be awarded ‘baby-friendly’ designation
-- School of Pharmacy undertakes initiative to help campus go green
-- Prayer breakfast commemorates presidential inauguration
-- Death Valley National Park makes for nice weekend trip
-- Loma Linda University makes efforts to go green
-- …

Diurnal Variation Of The Human Adipose Transcriptome And The Link To Metabolic Disease., Andrey Loboda, Walter K. Kraft, Bernard Fine, Jeffrey Joseph, Michael Nebozhyn, Chunsheng Zhang, Yudong He, Xia Yang, Christopher Wright, Mark Morris, Ira Chalikonda, Mark Ferguson, Valur Emilsson, Amy Leonardson, John Lamb, Hongyue Dai, Eric Schadt, Howard E. Greenberg, Pek Yee Lum

Department of Anesthesiology Faculty Papers

ABSTRACT: BACKGROUND: Circadian (diurnal) rhythm is an integral part of the physiology of the body; specifically, sleep, feeding behavior and metabolism are tightly linked to the light-dark cycle dictated by earth's rotation. METHODS: The present study examines the effect of diurnal rhythm on gene expression in the subcutaneous adipose tissue of overweight to mildly obese, healthy individuals. In this well-controlled clinical study, adipose biopsies were taken in the morning, afternoon and evening from individuals in three study arms: treatment with the weight loss drug sibutramine/fasted, placebo/fed and placebo/fasted. RESULTS: The results indicated that diurnal rhythm was the most significant driver …

The P53-Induced Siva-1 Plays A Significant Role In Cisplatin-Mediated Apoptosis, John L. Barkinge, Radhika Gudi, Hawkins Sarah, Fei Chu, Alip Borthakur, Bellur S. Prabhakar

Clinical & Translational Sciences

Background: The pro-apoptotic protein Siva-1 functions in both extrinsic and intrinsic cell death signaling; however, the exact contribution of the endogenous Siva-1 to DNA damage-induced apoptosis is unclear. Using cisplatin, a chemotherapeutic drug, to induce DNA damage and cell death, we determined the role of Siva-1.

Methods: Cisplatin treated HCT116 colorectal carcinoma cells (p53+/+ and -/-) were used in the study. With the help of recombinant lentivirus that can express siSiva (siRNA that specifi cally targets Siva-1), we also generated Siva-1 knockdown HCT116 cells. Apoptosis was determined by tetramethyl rhodamine methyl ester (TMRM) staining and propidium iodide (PI) staining.

Results: …

Alcohol And Cardio-Respiratory Deaths In Chinese: A Population-Based Case-Control Study Of 32,462 Older Hong Kong, Mary Schooling, Tai Hing Lam, Sai Yin Ho, Yao He, Kwok Hang Mak, Gabriel M. Leung

Publications and Research

Background
In observational studies moderate alcohol use reduces cardio-respiratory mortality. However observational studies may be biased by many factors including residual confounding by unmeasured differences between moderate alcohol users and other groups or by changes in alcohol use with ill-health and aging. We used two different analytic strategies in an under-studied population, i.e. southern Chinese, to provide an assessment of the specific impact of moderate alcohol use on mortality from ischemic heart disease (IHD) and chronic obstructive pulmonary diseases (COPD).

Methods
In a population-based case-control study of all adult deaths in Hong Kong Chinese in 1998, we used adjusted logistic …

Submicroscopic Gametocytes And The Transmission Of Antifolate-Resistant Plasmodium Falciparum In Western Kenya, Mayke J.A.M. Oesterholt, Michael Alifrangis, Colin J. Sutherland, Sabah A. Omar, Patrick Sawa, Christina Howitt, Louis C. Gouagna, Robert W. Sauerwein, Teun Bousema

All Peer-Reviewed Publications

Background: Single nucleotide polymorphisms (SNPs) in the dhfr and dhps genes are associated with sulphadoxine-pyrimethamine (SP) treatment failure and gametocyte carriage. This may result in enhanced transmission of mutant malaria parasites, as previously shown for chloroquine resistant parasites. In the present study, we determine the association between parasite mutations, submicroscopic P. falciparum gametocytemia and malaria transmission to mosquitoes. Methodology/Principal Findings: Samples from children treated with SP alone or in combination with artesunate (AS) or amodiaquine were genotyped for SNPs in the dhfr and dhps genes. Gametocytemia was determined by microscopy and Pfs25 RNA-based quantitative nucleic acid sequence-based amplification (Pfs25 QT-NASBA). …

Hollen, Linda Interview For The Miami Valley College Of Nursing And Health Oral History Project, Carol Holdcraft, Donna M. Curry, Linda Hollen

Wright State University - Miami Valley College of Nursing and Health Oral History Project

Carol Holdcraft and Donna Miles Curry interviewed Linda Hollen on February 4, 2009 about the founding of the Wright State University College of Nursing and Health. In the interview, Hollen discusses her career and her decision to come to Wright State as a student with the College of Nursing and Health.

Facilitated Monocyte-Macrophage Uptake And Tissue Distribution Of Superparmagnetic Iron-Oxide Nanoparticles., Arnaud Beduneau, Zhiya Ma, Cassi B. Grotepas, Alexander Kabanov, Barrett E. Rabinow, Nan Gong, R. Lee Mosley, Huanyu Dou, Michael D. Boska, Howard Gendelman

Journal Articles: Radiology

BACKGROUND: We posit that the same mononuclear phagocytes (MP) that serve as target cells and vehicles for a host of microbial infections can be used to improve diagnostics and drug delivery. We also theorize that physical and biological processes such as particle shape, size, coating and opsonization that affect MP clearance of debris and microbes can be harnessed to facilitate uptake of nanoparticles (NP) and tissue delivery.

METHODS: Monocytes and monocyte-derived macrophages (MDM) were used as vehicles of superparamagnetic iron oxide (SPIO) NP and immunoglobulin (IgG) or albumin coated SPIO for studies of uptake and distribution. IgG coated SPIO was …

Ada News - 02/02/2009, American Dental Association, Publishing Division

ADA News

Established in 1970 as the official newspaper of the American Dental Association, the ADA News serves practicing dentists and others allied to the dental profession in the U.S. and internationally. It is the No. 1 source of news and information about the many benefits and services the ADA delivers to members daily as well as timely information on scientific, social, political and economic developments affecting dentistry and health care.

Webb, Frank, 1906-1950 (Sc 1846), Manuscripts & Folklife Archives

Manuscript Collection Finding Aids

Finding aid and scan (Click on "Additional Files" below) for Manuscripts Small Collection 1846. Letter, 3 February 1930, from Frank Webb, a chiropractor in Irvine, Estill County, Kentucky, to an unnamed recipient discussing the death of a Mr. Chaney, a booster of chiropractic treatment.

Zebrafish Kidney Phagocytes Utilize Macropinocytosis And Ca+-Dependent Endocytic Mechanisms., Claudia Hohn, Sang-Ryul Lee, Lesya M. Pinchuk, Lora Petrie-Hanson

CVM Publications

BACKGROUND: The innate immune response constitutes the first line of defense against invading pathogens and consists of a variety of immune defense mechanisms including active endocytosis by macrophages and granulocytes. Endocytosis can be used as a reliable measure of selective and non-selective mechanisms of antigen uptake in the early phase of an immune response. Numerous assays have been developed to measure this response in a variety of mammalian and fish species. The small size of the zebrafish has prevented the large-scale collection of monocytes/macrophages and granulocytes for these endocytic assays. METHODOLOGY/PRINCIPAL FINDINGS: Pooled zebrafish kidney hematopoietic tissues were used as …

Interconnections Between Sigma B, Agr, And Proteolytic Activity In Staphylococcus Aureus Biofilm Maturation, Katherine J. Lauderdale, Blaise R. Boles, Ambrose L. Cheung, Alexander R. Horswill

Dartmouth Scholarship

Staphylococcus aureus is a proficient biofilm former on host tissues and medical implants. We mutagenized S. aureus strain SH1000 to identify loci essential for ica-independent mechanisms of biofilm maturation and identified multiple insertions in the rsbUVW-sigB operon. Following construction and characterization of a sigB deletion, we determined that the biofilm phenotype was due to a lack of sigma factor B (SigB) activity. The phenotype was conserved in a sigB mutant of USA300 strain LAC, a well-studied community-associated methicillin-resistant S. aureus isolate. We determined that agr RNAIII levels were elevated in the sigB mutants, and high levels of RNAIII expression are …

Integrative Health Studies Newsletter, Ciis

Integrative Health Studies Newsletter

This is the Feb-March 2009 issue of the Integrative Health Studies Newsletter at CIIS.

Genetic Contribution To Patent Ductus Arteriosus In The Premature Newborn, Naveed Hussain

Articles - Patient Care

BACKGROUND The most common congenital heart disease in the newborn population, patent ductus arteriosus, accounts for significant morbidity in preterm newborns. In addition to prematurity and environmental factors, we hypothesized that genetic factors play a significant role in this condition. OBJECTIVE The objective of this study was to quantify the contribution of genetic factors to the variance in liability for patent ductus arteriosus in premature newborns. PATIENTS AND METHODS A retrospective study (1991–2006) from 2 centers was performed by using zygosity data from premature twins born at ≤36 weeks’ gestational age and surviving beyond 36 weeks’ postmenstrual age. Patent ductus …

Alcohol In Moderation, Cardioprotection And Neuroprotection : Epidemiological Considerations And Mechanistic Studies, Dipak K. Das Dr.

UCHC Articles - Research

In contrast to many years of important research and clinical attention to the pathological effects of alcohol (ethanol) abuse, the past several decades have seen the publication of a number of peer-reviewed studies indicating beneficial effects of light-moderate, non-binge consumption of varied alcoholic beverages, as well as experimental demonstrations that moderate alcohol exposure can initiate typically cytoprotective mechanisms. A considerable body of epidemiology associates moderate alcohol consumption with significantly reduced risks of coronary heart disease and, albeit currently a less robust relationship, cerebrovascular (ischemic) stroke. Experimental studies with experimental rodent models and cultures (cardiac myocytes, endothelial cells) indicate that moderate …

Identification Of Novel Tumor Antigens With Patient-Derived Immune-Selected Antibodies, Daniel Rodriguez-Pinto, Martin P. Keough, Kathryn N. Phoenix, Frank Vumbaca, David K. K. Han, Kevin P. Claffey

UCHC Articles - Research

The identification of tumor antigens capable of eliciting an immune response in vivo may be an effective method to identify therapeutic cancer targets. We have developed a method to identify such antigens using frozen tumor-draining lymph node samples from breast cancer patients. Immune responses in tumor-draining lymph nodes were identified by immunostaining lymph node sections for B-cell markers (CD20&CD23) and Ki67 which revealed cell proliferation in germinal center zones. Antigen-dependent somatic hypermutation (SH) and clonal expansion (CE) were present in heavy chain variable (VH) domain cDNA clones obtained from these germinal centers, but not from Ki67 negative germinal centers. Recombinant …

Human Cyt P450 Mediated Metabolic Toxicity Of 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanone (Nnk) Evaluated Using Electrochemiluminescent Arrays, Sadagopan Krishnan, Besnik Bajrami, John B. Schenkman, James F. Rusling

UCHC Articles - Research

Electrochemiluminescent (ECL) arrays containing polymer ([Ru(bpy)₂(PVP)₁₀]²⁺, PVP = polyvinylpyridine), DNA, and selected enzymes were employed to elucidate cytochrome (cyt) P450 dependent metabolism of the tobacco specific carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Bioactivated NNK metabolites formed upon H₂O₂-enzymatic activation were captured as DNA adducts and detected simultaneously from 36 spot arrays by capturing and quantifying emitted ECL with an overhead CCD camera. Increased ECL emission was dependent on NNK exposure time. Of the enzymes tested, the activity toward NNK bioactivation was cyt P450 1A2 > 2E1 > 1B1 ≈ chloroperoxidase (CPO) > myoglobin (Mb) in accordance …

Remission And Recovery In The Treatment For Adolescents With Depression Study (Tads): Acute And Long-Term Outcomes., Betsy D. Kennard, Susan G. Silva, Simon Tonev, Paul Rohde, Jennifer L. Hughes, Benedetto Vitiello, Christopher J. Kratochvil, John F. Curry, Graham J. Emslie, Mark Reinecke, John March

Journal Articles: Psychiatry

OBJECTIVE: We examine remission rate probabilities, recovery rates, and residual symptoms across 36 weeks in the Treatment for Adolescents with Depression Study (TADS).

METHOD: The TADS, a multisite clinical trial, randomized 439 adolescents with major depressive disorder to 12 weeks of treatment with fluoxetine, cognitive-behavioral therapy, their combination, or pill placebo. The pill placebo group, treated openly after week 12, was not included in the subsequent analyses. Treatment differences in remission rates and probabilities of remission over time are compared. Recovery rates in remitters at weeks 12 (acute phase remitters) and 18 (continuation phase remitters) are summarized. We also examined …

London City Life: A Call To Service, Mary Ann Colohan

Data and Test Instruments

London and the University of Western Ontario have a strong tradition of sending medical personnel to war. Afghanistan is no exception.

Accumulation Of Artemisinin Trioxane Derivatives Within Neutral Lipids Of Plasmodium Falciparum Malaria Parasites Is Endoperoxide-Dependent, Carmony L. Hartwig, Andrew S. Rosenthal, John D'Angelo, Carol E. Griffin, Gary H. Posner, Roland A. Cooper

Collected Faculty Scholarship

The antimalarial trioxanes, exemplified by the naturally occurring sesquiterpene lactone artemisinin and its semi-synthetic derivatives, contain an endoperoxide pharmacophore that lends tremendous potency against Plasmodium parasites. Despite decades of research, their mechanism of action remains unresolved. A leading model of anti-plasmodial activity hypothesizes that iron-mediated cleavage of the endoperoxide bridge generates cytotoxic drug metabolites capable of damaging cellular macromolecules. To probe the malarial targets of the endoperoxide drugs, we studied the distribution of fluorescent dansyl trioxane derivatives in living, intraerythrocytic-stage Plasmodium falciparum parasites using microscopic imaging. The fluorescent trioxanes rapidly accumulated in parasitized erythrocytes, localizing within digestive vacuole-associated neutral lipid …

Preparing For Cne Certification: A Journey To Excellence, Dawn Garrett-Wright, Crista Briggs, Cathy H. Abell

Nursing Faculty Publications

No abstract provided.